Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

A.A.M. (Sylvia) Genet; E. Visser; Ben E.E.M. van den Borne; Maggy Youssef El Soud; Huub Belderbos; Gerben Stege; Marleen de Saegher; Federica Eduati; Maarten A.C. Broeren; Joost L.J. van Dongen; Luc Brunsveld; Daan H. van de Kerkhof; Volkher Scharnhorst

doi:10.18632/oncotarget.27664

Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

A.A.M. (Sylvia) Genet, E. Visser, Ben E.E.M. van den Borne, Maggy Youssef El Soud, Huub Belderbos, Gerben Stege, Marleen de Saegher, Federica Eduati, Maarten A.C. Broeren, Joost L.J. van Dongen, Luc Brunsveld, Daan H. van de Kerkhof (Corresponding author), Volkher Scharnhorst

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Abstract

Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis,
prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics.
Two serum pools were spiked with increasing amounts of hemolysate obtained
from multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.
Therefore, a hemolysis correction equation should be used to correct falsely
elevated NSE concentrations. Results of samples with an H-index above 30 μmol/L
should not be reported to clinicians. Application of the equation illustrates the
importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

Original language	English
Pages (from-to)	2660-2668
Number of pages	9
Journal	Oncotarget
Volume	11
Issue number	27
DOIs	https://doi.org/10.18632/oncotarget.27664
Publication status	Published - 7 Jul 2020

Keywords

Hemolysis correction equation
Neuron-specific enolase
Protein tumor markers
Small-cell lung cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.27664Licence: CC BY

27664-1056449-1-PBFinal published version, 1.6 MB

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Genet, A. A. M., Visser, E., van den Borne, B. E. E. M., El Soud, M. Y., Belderbos, H., Stege, G., de Saegher, M., Eduati, F., Broeren, M. A. C., van Dongen, J. L. J., Brunsveld, L., van de Kerkhof, D. H., & Scharnhorst, V. (2020). Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer. Oncotarget, 11(27), 2660-2668. https://doi.org/10.18632/oncotarget.27664

@article{69cea5939cea4670af52526caff32a2b,

title = "Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer",

abstract = "Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis,prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics.Two serum pools were spiked with increasing amounts of hemolysate obtainedfrom multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.Therefore, a hemolysis correction equation should be used to correct falselyelevated NSE concentrations. Results of samples with an H-index above 30 μmol/Lshould not be reported to clinicians. Application of the equation illustrates theimportance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.",

keywords = "Hemolysis correction equation, Neuron-specific enolase, Protein tumor markers, Small-cell lung cancer",

author = "Genet, {A.A.M. (Sylvia)} and E. Visser and {van den Borne}, {Ben E.E.M.} and {El Soud}, {Maggy Youssef} and Huub Belderbos and Gerben Stege and {de Saegher}, Marleen and Federica Eduati and Broeren, {Maarten A.C.} and {van Dongen}, {Joost L.J.} and Luc Brunsveld and {van de Kerkhof}, {Daan H.} and Volkher Scharnhorst",

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month = jul,

day = "7",

doi = "10.18632/oncotarget.27664",

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Genet, AAM, Visser, E, van den Borne, BEEM, El Soud, MY, Belderbos, H, Stege, G, de Saegher, M, Eduati, F , Broeren, MAC , van Dongen, JLJ , Brunsveld, L , van de Kerkhof, DH & Scharnhorst, V 2020, 'Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer', Oncotarget, vol. 11, no. 27, pp. 2660-2668. https://doi.org/10.18632/oncotarget.27664

TY - JOUR

T1 - Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

AU - Genet, A.A.M. (Sylvia)

AU - Visser, E.

AU - van den Borne, Ben E.E.M.

AU - El Soud, Maggy Youssef

AU - Belderbos, Huub

AU - Stege, Gerben

AU - de Saegher, Marleen

AU - Eduati, Federica

AU - Broeren, Maarten A.C.

AU - van Dongen, Joost L.J.

AU - Brunsveld, Luc

AU - van de Kerkhof, Daan H.

AU - Scharnhorst, Volkher

PY - 2020/7/7

Y1 - 2020/7/7

N2 - Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis,prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics.Two serum pools were spiked with increasing amounts of hemolysate obtainedfrom multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.Therefore, a hemolysis correction equation should be used to correct falselyelevated NSE concentrations. Results of samples with an H-index above 30 μmol/Lshould not be reported to clinicians. Application of the equation illustrates theimportance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

AB - Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis,prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics.Two serum pools were spiked with increasing amounts of hemolysate obtainedfrom multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.Therefore, a hemolysis correction equation should be used to correct falselyelevated NSE concentrations. Results of samples with an H-index above 30 μmol/Lshould not be reported to clinicians. Application of the equation illustrates theimportance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

KW - Hemolysis correction equation

KW - Neuron-specific enolase

KW - Protein tumor markers

KW - Small-cell lung cancer

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U2 - 10.18632/oncotarget.27664

DO - 10.18632/oncotarget.27664

M3 - Article

C2 - 32676167

SN - 1949-2553

VL - 11

SP - 2660

EP - 2668

JO - Oncotarget

JF - Oncotarget

IS - 27

ER -

Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

Abstract

Keywords

UN SDGs

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Oncotarget: Correction of NSE concentration improves diagnostic accuracy in lung cancer

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Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

Abstract

Keywords

UN SDGs

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Oncotarget: Correction of NSE concentration improves diagnostic accuracy in lung cancer

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